Non-Genoidentical Donor Stem Cell Transplantation for Fanconi Anemia: Good Risk Regimen
Date Last Modified: 2003-08
Date First Published: 2003-08-13
Basic Study Information
| Type of Trial | Status of Trial | Age Range (yrs.) | Sponsor of Trial | Protocol IDs |
|---|
| Treatment | Active | Less than 30 years | CCHMC | 03-01-48 |
Objectives
- Evaluate the efficacy in achieving engraftment in Fanconi anemia (FA) recipients of unrelated donor peripheral blood stem cells that have undergone T-cell depletion using the Isolex 300i column, and using a preparative regimen of TBI/Fludarabine/Cyclophosphamide/ATG.
- Evaluate the incidence of GVHD, regimen-related toxicity and disease-free survival.
Entry Criteria
Disease Characteristics:
- Diagnosis of Fanconi anemia confirmed by studies of peripheral blood chromosomes incubated in an alkylating agent such as mitomycin-C or DEB. Diagnosis must have been confirmed through DEB testing performed in Dr. Auerbach's laboratory (Rockefeller University).
Prior/Concurrent Therapy:
Biologic therapy:
- One of the following must be true:
Patient must have evidence of severe cytopenias manifested by: - Absolute neutrophil count (ANC) <1000/ml3 on or off G-CSF, or
- Hemoglobin<8 gm/dl on or off erythropoietin, or
- Platelet count < 50,000/ml3, or
- Requiring blood product transfusions on a regular basis
-OR
Show evidence of progression to myelodysplasia by any of the following on testing of the marrow: - Morphologic features of myelodysplastic syndrome
- Presence of a cytogenetic clone together with dysplasia
-OR-
Marrow asplasia or early MDS [RA or RAEB (<10% blasts)]
Chemotherapy:
Endocrine therapy:
Radiotherapy:
Surgery:
Other:
- No prior invasive fungal infection
- No prior gram negative sepsis
- No available 6 antigen (A, B, and DRB1) matched sibling donor
- A fully matched (6/6: A, B, and DRB1) or one antigen mismatched (5/6) unrelated peripheral blood stem cell donor must be available. Peripheral blood stem cells with a target CD 34+ cell dose of 5 x 106/kg will be required. If a suitable donor is not available, umbilical cord blood matched at 6/6, 5/6 or 4/6 loci can be used if the cell dose is adequate (>3.5 x 107/kg). Umbilical cord blood will undergo no T cell depletion via the Isolex column. All patients and potential donors will be typed by high-resolution techniques for A,B, C, and DRB1 to aid in the choice of donor. Marrow will not be accepted as a source of cells.
- Recipients with a 5/6 antigen matched family member donor or a 6/6 matched non-sibling family member donor are also eligible for treatment according to this protocol. Peripheral blood stem cells are the only acceptable stem cell source for this protocol.
Patient Characteristics:
Age:
- Less than 30 years at time of transplant
Performance status:
Life expectancy:
- A life expectancy of > 3 months
Hematopoietic:
- Early stage disease which meets the hematological criteria described above
Hepatic:
- Bilirubin <2 times upper limit of normal
- AST <3 times upper limit of normal
- ALT <3 times upper limit of normal
- Alkaline Phosphotase <3 times upper limit of normal
Renal:
Cardiovascular:
- Shortening fraction > 25%
Pulmonary:
- No clinically significant pulmonary compromise or oxygen requirement
Neurologic:
Other:
- No other organ dysfunction deemed by the attending physician to preclude a full preparative regimen
- Availability of an acceptable donor
- Signed informed consent or ability to undergo informed consent process
- No active infection within one week of BMT
- No female who is pregnant or lactating
- HIV negative
Projected Accrual
A total of 35 patients will be accrued for this study.
Outline
The purpose of this study is to investigate the use of cyclophosphamide (CTX) and total body irradiation (TBI) combined with fludarabine in the transplantation of patients with Fanconi anemia (FA) who lack a matched sibling donor. Patients will receive unrelated donor peripheral blood stem cells (PBSC) that have undergone T-cell depletion (TCD) by use of the Isolex 300i column to prevent graft versus host disease (GVHD) as GVHD is poorly tolerated in FA patients (4). These patients will additionally receive anti-thymocyte globulin (ATGAM) in an attempt to prevent graft rejection. Data from others has shown that patients can be clinically categorized into good risk and poor risk cases with large differences in outcome in the two categories. This protocol will be utilized for patients whose cases are classified as "Good Risk."
